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Neutrophil extracellular traps promote peritoneal metastasis of colon cancer cells

Al-Haidari, Amr A. LU ; Algethami, Nader LU ; Lepsenyi, Mattias LU ; Rahman, Milladur LU ; Syk, Ingvar LU and Thorlacius, Henrik LU (2019) In Oncotarget 10(12). p.1238-1249
Abstract

Cytoreductive surgery is the only curative option for patients with peritoneal carcinomatosis, however, intraperitoneal recurrence rate is high making new ways to prevent cancer recurrence an urgent need. Recent evidence suggests that neutrophils are involved in cancer progression. The purpose of our study was to examine the role of neutrophils in the spread of colon cancer cells in the peritoneal cavity. The number of metastatic noduli in the peritoneal cavity was quantified in mice injected with murine colon cancer cells (CT-26) intraperitoneally after surgical laparotomy and treated with a neutrophil depleting antibody or DNase I. In addition, peritoneal metastases were harvested from patients with peritoneal carcinomatosis. Scanning... (More)

Cytoreductive surgery is the only curative option for patients with peritoneal carcinomatosis, however, intraperitoneal recurrence rate is high making new ways to prevent cancer recurrence an urgent need. Recent evidence suggests that neutrophils are involved in cancer progression. The purpose of our study was to examine the role of neutrophils in the spread of colon cancer cells in the peritoneal cavity. The number of metastatic noduli in the peritoneal cavity was quantified in mice injected with murine colon cancer cells (CT-26) intraperitoneally after surgical laparotomy and treated with a neutrophil depleting antibody or DNase I. In addition, peritoneal metastases were harvested from patients with peritoneal carcinomatosis. Scanning and transmission electron microscopy showed extensive neutrophil extracellular trap (NET) formation in peritoneal colon cancer metastases in mice and patients. Neutrophil depletion markedly reduced the number of metastases in laparotomised animals. Administration of DNase I decreased the number of metastatic nodules by 88% in laparotomised animals as well as NET-induced chemokinedependent colon cancer cell migration and adhesion in vitro. Finally, CT-26 cancer cells were found to express the avβ3 integrin and inhibition of av integrin abolished NET-induced adhesion of colon cancer cells to vitronectin. Taken together, our data show that NETs play an important role in colon cancer cell metastasis in the peritoneal cavity and regulate colon cancer cell migration and adhesion to extracellular matrix proteins. These novel findings suggest that targeting NETs might be an effective strategy to antagonize intrabdominal recurrences of colon cancer after cytoreductive surgery in patients with peritoneal carcinomatosis.

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organization
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type
Contribution to journal
publication status
published
subject
keywords
Carcinomatosis, Chemokines, Metastases, Neutrophils, Peritoneum
in
Oncotarget
volume
10
issue
12
pages
12 pages
publisher
Impact Journals, LLC
external identifiers
  • scopus:85061363244
ISSN
1949-2553
DOI
10.18632/oncotarget.26664
language
English
LU publication?
yes
id
fb412bec-e256-402e-a806-3f764ad152ab
date added to LUP
2019-02-19 10:25:37
date last changed
2019-10-15 06:58:54
@article{fb412bec-e256-402e-a806-3f764ad152ab,
  abstract     = {<p>Cytoreductive surgery is the only curative option for patients with peritoneal carcinomatosis, however, intraperitoneal recurrence rate is high making new ways to prevent cancer recurrence an urgent need. Recent evidence suggests that neutrophils are involved in cancer progression. The purpose of our study was to examine the role of neutrophils in the spread of colon cancer cells in the peritoneal cavity. The number of metastatic noduli in the peritoneal cavity was quantified in mice injected with murine colon cancer cells (CT-26) intraperitoneally after surgical laparotomy and treated with a neutrophil depleting antibody or DNase I. In addition, peritoneal metastases were harvested from patients with peritoneal carcinomatosis. Scanning and transmission electron microscopy showed extensive neutrophil extracellular trap (NET) formation in peritoneal colon cancer metastases in mice and patients. Neutrophil depletion markedly reduced the number of metastases in laparotomised animals. Administration of DNase I decreased the number of metastatic nodules by 88% in laparotomised animals as well as NET-induced chemokinedependent colon cancer cell migration and adhesion in vitro. Finally, CT-26 cancer cells were found to express the avβ3 integrin and inhibition of av integrin abolished NET-induced adhesion of colon cancer cells to vitronectin. Taken together, our data show that NETs play an important role in colon cancer cell metastasis in the peritoneal cavity and regulate colon cancer cell migration and adhesion to extracellular matrix proteins. These novel findings suggest that targeting NETs might be an effective strategy to antagonize intrabdominal recurrences of colon cancer after cytoreductive surgery in patients with peritoneal carcinomatosis.</p>},
  author       = {Al-Haidari, Amr A. and Algethami, Nader and Lepsenyi, Mattias and Rahman, Milladur and Syk, Ingvar and Thorlacius, Henrik},
  issn         = {1949-2553},
  keyword      = {Carcinomatosis,Chemokines,Metastases,Neutrophils,Peritoneum},
  language     = {eng},
  number       = {12},
  pages        = {1238--1249},
  publisher    = {Impact Journals, LLC},
  series       = {Oncotarget},
  title        = {Neutrophil extracellular traps promote peritoneal metastasis of colon cancer cells},
  url          = {http://dx.doi.org/10.18632/oncotarget.26664},
  volume       = {10},
  year         = {2019},
}